Objective To evaluate DNA and RNA oxidation in diabetes mellitus.Methods We used a sensitive and accurate method based on isotope dilution high-performance liquid chromatography-triple quadruple mass spectrometry (ID-LC-MS/MS) to determine the levels of 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosin (8-oxo-Gsn) in various tissue specimens,plasma and urine of hyperglycemic SD rats induced by streptozotocin (STZ).Results The oxidative DNA and RNA damage were observed in various organs and the amounts of 8-oxo-dGsn and 8-oxo-Gsn derived from DNA and RNA were increased with hyperglycemic status.The levels of 8-oxo-Gsn in urine and plasma were significantly higher compared to that of 8-oxo-dGsn,which most likely reflected the RNA damage that occurs more frequently compared to DNA damage.Conclusion For the oxidative stress induced by hyperglycemia,8-oxo-Gsn in urine may be a sensitive biomarker based on the results in urine,plasma and tissues.%目的 评估高血糖对DNA和RNA氧化损伤的影响.方法 以链脲佐菌素诱导的糖尿病大鼠为模型,运用放射性核素稀释高效液相-串联质谱(ID-LC-MS/MS)法检测大鼠肾性、心性、肝性、肺、脑、睾丸、附睾、血浆和尿中的核酸氧化标志物8-氧化脱氧鸟苷(8-oxo-dGsn)和8-氧化鸟苷(8-oxo-Gsn)的含量,并进行比较分析.结果 虽然不同脏器DNA中8-oxo-dGsn/106 dGsn和RNA中8-oxo-Gsn/106Gsn的基础水平不一致,但是模型组SD大鼠不同脏器中8-oxo-Gsn/106Gsn和8-oxo-dGsn/106dGsn的水平均高于对照组,6月组糖尿病大鼠肾脏、肺脏和睾丸中8-oxo-dGsn/106dGsn的水平高于对照组相应脏器的水平(P＜0.05);3月组糖尿病大鼠肾脏、心脏和睾丸中8-oxo-Gsn/106Gsn的水平高于对照组相应脏器的水平(P＜0.05);除了脑和肺脏,6月组糖尿病大鼠各脏器中8-oxo-Gsn/106Gsn的水平均高于其对照组(P＜0.05);糖尿病大鼠血浆8-oxo-dGsn和8-oxo-Gsn浓度明显高于其同龄对照大鼠,且随着高糖血症的持续而增加.尿液检测结果的趋势与血浆中的检测结果一致,RNA氧化代谢产物8-oxo-Gsn均高于DNA的氧化代谢产物8-oxo-dGsn.结论 高血糖引起的氧化应激增强可以造成多器官DNA和RNA氧化损伤增加,DNA和RNA氧化损伤随着高糖血症的持续而增加;RNA氧化损伤水平高于DNA氧化损伤,其标志物尿液8-oxo-Gsn可以作为评估糖尿病氧化应激状态的良好指标.
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